| Autor: |
Onubogu U; The Skaggs Graduate School of Chemical and Biological Science, The Scripps Research Institute, La Jolla, California, USA.; Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, Florida, USA., Gatenbee CD; Department of Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA., Prabhakaran S; Department of Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA., Wolfe KL; The Skaggs Graduate School of Chemical and Biological Science, The Scripps Research Institute, La Jolla, California, USA.; Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, Florida, USA., Oakes B; Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, Florida, USA., Salatino R; The Skaggs Graduate School of Chemical and Biological Science, The Scripps Research Institute, La Jolla, California, USA.; Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, Florida, USA., Vaubel R; Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Rochester, Minnesota, USA., Szentirmai O; Center for Neurological Surgery and Neuroscience, Cleveland Clinic Martin Health, Port St. Lucie, Florida, USA., Anderson AR; Department of Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA., Janiszewska M; The Skaggs Graduate School of Chemical and Biological Science, The Scripps Research Institute, La Jolla, California, USA.; Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, Florida, USA. |
| Abstrakt: |
Tumor evolution is driven by genetic variation; however, it is the tumor microenvironment (TME) that provides the selective pressure contributing to evolution in cancer. Despite high histopathological heterogeneity within glioblastoma (GBM), the most aggressive brain tumor, the interactions between the genetically distinct GBM cells and the surrounding TME are not fully understood. To address this, we analyzed matched primary and recurrent GBM archival tumor tissues with imaging-based techniques aimed to simultaneously evaluate tumor tissues for the presence of hypoxic, angiogenic, and inflammatory niches, extracellular matrix (ECM) organization, TERT promoter mutational status, and several oncogenic amplifications on the same slide and location. We found that the relationships between genetic and TME diversity are different in primary and matched recurrent tumors. Interestingly, the texture of the ECM, identified by label-free reflectance imaging, was predictive of single-cell genetic traits present in the tissue. Moreover, reflectance of ECM revealed structured organization of the perivascular niche in recurrent GBM, enriched in immunosuppressive macrophages. Single-cell spatial transcriptomics further confirmed the presence of the niche-specific macrophage populations and identified interactions between endothelial cells, perivascular fibroblasts, and immunosuppressive macrophages. Our results underscore the importance of GBM tissue organization in tumor evolution and highlight genetic and spatial dependencies. |
